[Nanolysis]

Hello guys,

I'm a first year student in biopharmaceutical scienes and orgainc chemistry is a course we need to get through. In a few days I'll have to make the exam again because I failed the first exam horribly.

So I'm studying again and I really experience problems with stereochemistry and one other reaction I encountered.

Some things are still not clear to me.

So I have to determine what relations these two compounds have (see picture)


I'd say they're diastereomeres because only one stereocenter is the same in both and 2 are different?

And I'm also asked if we'd treat both compounds with DBU (the picture is way too big for the thread) http://www.iris-biotech.de/media/catalog/product/cache/2/image/9df78eab33525d08d6e5fb8d27136e95/r/l/rl-1151_182.jpg only one would react with it.

But how can I know this? I do understand the pi bond from the double bond in DBU will attack a proton from both compounds. But which proton exactly and how can I distinguish their reactivity?

And a second question I have: the following compound is treated with sulfuric acid and a Grignard reagent.
 

These are the reactants, the product is given in a molecular formula and I'm ought to give the structural formula of the synthesized compound...I really can't explain the product. The only thing I know is that they're two oxygens lost and that they must become a good leaving group first before they can be cleaved off....this is done with protonation of both carbonlyl groups right? Not the ester-oxygen...but what is the mechanism exactly?

Can anyone help me?

[kriggy]

1) I think the first two compounds have two centers which are same (they have only difference at the right methyl group)
the reaction with DBU has probably something to do with steric hinderance of OTs group?

2) how many carbon atoms you need to add to your starting material to have same amount of carbons as in your product? Do you know grignard reaction? Where can the MeMgBr react in your starting molecule?

[izchief360]

Ok, so here's how I see it.

You need to consider stereochemistry and steric hinderance. In the A and B molecules, the only difference is the direction in which the methyl group faces. You are correct in thinking that these two are diastereomers, now let's consider their reaction with DBU.

First of all, tosylates are a great leaving group (can distribute the resulting negative charge very well). Second, DBU is a fairly bulky molecule. When considering Molecule B, the tosylate is facing the same direction as the methyl group on the right. In this case, DBU has a hard time attacking the ring carbon bound to the tosylate because the methyl is "blocking" it.

In the case of Molecule A however, neither of the methyl groups are facing the same direction as the tosylate group, so DBU is free to attack the ring carbon and the reaction can proceed. This is the molecule that will react with DBU.

In the case of the reaction, I've attached what I predict will happen (I'm one O off). Basically, you need to view the molecule as two parts. There is an ester on the right end, and an aldehyde on the left end. A grignard will react at both of these carbons. At the ester end, it will displace the ester group with two R groups (where R is the substituent on the grignard) and make the carbonyl into an alcohol. You get a 3degree alcohol. At the aldehyde end, it will react and produce a 2 degree alcohol.

More info on the mechanisms: http://www.masterorganicchemistry.com/2011/04/14/why-organic-chemistry-is-hard-2/

At the moment, I can't figure out how they are getting rid of two oxygens. I only see one (the one from the ester) leaving the molecule. Anyways, hope this helps in some ways. I'll respond later if I come up with anything.

[Dan]

Re: steric hinderance in DBU elimination. I think this is mainly a stereoelectronic effect - you must consider the stereochemical requirements of E2 and compare the reactive conformation of each isomer. Hint: Draw lots of chairs.

[critzz]

At the moment, I can't figure out how they are getting rid of two oxygens.

I think in this case H₂SO₄ will not only neutralize the grignard product, but will also induce a E1-elimination of the formed alcohol (due to a very stable carbocation).

[orgopete]

For the first reaction, you must consider the stereochemistry of elimination reactions, they are anti-periplanar. The proton and leaving group must be on opposite sides.